The immune system is required for defending the host against infections. However, immune responses are themselves capable of causing tissue injury and disease. Injurious, or pathologic, immune reactions are called hypersensitivity reactions. This term is derived from the idea that an immune response to an antigen may result in sensitivity to challenge with that antigen and, therefore, hypersensitivity is a reflection of excessive or aberrant immune responses. Hypersensitivity reactions may occur in two situations. First, responses to foreign antigens may be dysregulated or uncontrolled, resulting in tissue injury. Second, the immune responses may be directed against self (autologous) antigens, as a result of the failure of self-tolerance. Responses against self antigens are termed autoimmunity, and disorders caused by such responses are called autoimmune diseases.
Much of the damage resulting from inflammation is due to a shift in the polarization of macrophage M1 and M2 phenotypes. M1 macrophages produce copious amounts of reactive oxygen and nitrogen intermediates and inflammatory cytokines; are part of the afferent and efferent limb of polarized Th1 responses; and mediate resistance against intracellular parasites and tumors. M2 cells are generally involved in the T helper 2 (Th2) response; have immunoregulatory function; orchestrate encapsulation and containment of parasites; and promote tissue repair, remodeling, and tumor progression. Therefore, whereas M1 macrophages are generally destructive, M2 macrophages are generally reparative.
It is therefore an object of the invention to provide therapeutic compositions and methods for reducing inflammation in a tissue of a subject.
It is another object of the invention to provide compositions and methods for shifting the polarization of macrophages from an M1 phenotype to an M2 phenotype.
It is a further object of the invention to provide therapeutic compositions and methods for treating inflammatory diseases.